A carbocyclic nucleoside analogue is a TNF-alpha inhibitor with immunosuppressive action: role of prostaglandin E2 and protein kinase C and comparison with pentoxifylline.

Tumor necrosis factor-alpha (TNF-alpha) is associated with several acute and chronic inflammatory conditions. New therapies directed at inhibiting TNF-alpha will be important in treating pathological processes mediated by TNF-alpha. In this study, we studied and compared the effect of the carbocyclic nucleoside analogue (9-[(1R, 3R)-trans-cyclopentan-3-ol] adenine) with pentoxifylline on modulating TNF-alpha production.

MTS interferon assay: a simplified cellular dehydrogenase assay for interferon activity using a water-soluble tetrazolium salt.

MTS, a tetrazolium dye, is reduced by hydrogenases in living cells to a water-soluble formazan. When it is added to the medium at the end of a cytopathic effects (CPE) inhibition interferon assay, the formazan formed diffuses into the medium; the resultant optical density directly and quantitatively measures how much cellular damage has been produced by the challenge virus in the presence of different amounts of interferon. The use of MTS has considerable advantages in that after it is added, no further steps, such as washing of the cells, extraction of dye, or other manipulations, are needed.

Expression of a channel-like pathway for adenosine transport in Leishmania donovani promastigotes.

L. donovani promastigotes (MHOM/ET/67/HA3) transport adenosine by a route that is sensitive to inhibition by a nonspecific channel blocker, propranolol. At the logarithmic and stationary phases of growth, the transport of 1 microM-3H-adenosine was significantly inhibited (40-50%) by 100 microM-propranolol.

Nucleoside transporters in Leishmania major: diversity in adenosine transporter expression or function in different strains.

Cytotoxic nucleoside derivatives may become useful in the treatment of parasitic infections. As part of our drug development studies, the effect of a number of nucleosides (100 microM) on the cellular transport of 3H-adenosine and 3H-inosine (each at 1 microM) in promastigotes from four Leishmania major strains was investigated. When 3H-inosine was used as permeant, all strains exhibited essentially the same inhibition profile, with unlabeled inosine, guanosine, formycin B, and 3'-deoxyinosine being strongly inhibitory, and adenosine-related compounds such as 2'-deoxyadenosine and tubercidin being inactive.